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Pharmacokinetic and pharmacodynamic study of S-8117 (controlled-release oxycodone tablet) on opioid-naive patients with cancer-related pain
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European Journal of Pain (2001) 5 (Suppl. A): 133±134 doi:10.1053/eujp.2001.0300, available online at http://www.idealibrary.com on
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Pharmacokinetic and pharmacodynamic study of S-8117 (controlled-release oxycodone tablet) on opioid-naive patients with cancer-related pain W. Koizumi, S. Tanabe, S. Nagaba, K. Saigenji, M. Nonakaa and K. Yagoa Department of lnternal Medicine, School of Medicine, Kitasato University, Department of Pharmacy, a Kitasato University East Hospital, Japan
INTRODUCTION
RESULTS
In Japan, controlled-release oxycodone (Oxycontin$) is in development for registration by Shionogi Co, Ltd, under the code name S-8117. In addition to the tablet strengths of 10, 20, and 40 mg to be registered, it was decided to develop for the Japanese market also a 5 mg tablet for cancer pain treatment.
In the PK/PD phase, the mean values of pain intensity score measured by CAT and VAS are shown in Fig. 1. CAT value was 1.8 just before dosing; it decreased to 1.2 at 1 hour after dosing and remained 1.2 even 12 hours later. VAS value was 46 just before dosing and decreased to 38, 32, and 32 at time points 1, 5 and 12 hours after dosing, respectively. The mean blood level of oxycodone was 3.4 ng/ml and 4.4 ng/ml at 1 and 12 hours after dosing, respectively. Concerning the titration phase and the control phase, pain control was achieved in four out of five patients at a dose of 5 mg twice-daily and at 10 mg twice daily in one out of five patients. Although opioid-related typical adverse drug reactions such
METHOD Five patients who suffered from chronic cancer pain with non-steroidal anti-inflammatory drugs (NSAIDs) medication and had not received treatment with any opioids in the last 2 weeks were enrolled. They were given 5-mg tablets of S-8117 twice-daily. The blood level of oxycodone was monitored at six time points (0, 1, 3, 5, 8 and 12 hours) after the initial dosing (PK/PD phase). In addition, pain intensity was evaluated at the same time points by using CAT (0: none, 1: slight, 2: moderate, 3: severe) and VAS. The dose was increased until pain control was achieved (titration and control phase). The dosing of S-8117 was continued for 7 days.
Correspondence to: W. Koizumi, Department of Internal Medicine, School of Medicine, Kitasato University Department of Pharmacy, Kitasato, Japan.
FIG. 1. Plasma concentration of oxycodone and pain intensity in PK/PD phase.
1090-3801/01/0A0133 + 02 $35.00/0 & 2001 European Federation of Chapters of the International Association for the Study of Pain
Black plate (134,1)
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as nausea, vomiting, dizziness and constipation were observed, these were tolerable to the patients.
CONCLUSION Possible relationships between PK/PD could be obtained in this pilot study even at 5 mg twice-daily
European Journal of Pain (2001), 5 (Suppl. A)
W. KOIZUMI
ET AL .
for Japanese patients. Furthermore, analgesic efficacy was demonstrated to last over 12 hours with a quick onset of relief after dosing. As the same study has been conducted in other facilities, extensive results from this trial will become available soon.
European Journal of Pain (2001) 5 (Suppl. A): 133±134 doi:10.1053/eujp.2001.0300, available online at http://www.idealibrary.com on
1
Pharmacokinetic and pharmacodynamic study of S-8117 (controlled-release oxycodone tablet) on opioid-naive patients with cancer-related pain W. Koizumi, S. Tanabe, S. Nagaba, K. Saigenji, M. Nonakaa and K. Yagoa Department of lnternal Medicine, School of Medicine, Kitasato University, Department of Pharmacy, a Kitasato University East Hospital, Japan
INTRODUCTION
RESULTS
In Japan, controlled-release oxycodone (Oxycontin$) is in development for registration by Shionogi Co, Ltd, under the code name S-8117. In addition to the tablet strengths of 10, 20, and 40 mg to be registered, it was decided to develop for the Japanese market also a 5 mg tablet for cancer pain treatment.
In the PK/PD phase, the mean values of pain intensity score measured by CAT and VAS are shown in Fig. 1. CAT value was 1.8 just before dosing; it decreased to 1.2 at 1 hour after dosing and remained 1.2 even 12 hours later. VAS value was 46 just before dosing and decreased to 38, 32, and 32 at time points 1, 5 and 12 hours after dosing, respectively. The mean blood level of oxycodone was 3.4 ng/ml and 4.4 ng/ml at 1 and 12 hours after dosing, respectively. Concerning the titration phase and the control phase, pain control was achieved in four out of five patients at a dose of 5 mg twice-daily and at 10 mg twice daily in one out of five patients. Although opioid-related typical adverse drug reactions such
METHOD Five patients who suffered from chronic cancer pain with non-steroidal anti-inflammatory drugs (NSAIDs) medication and had not received treatment with any opioids in the last 2 weeks were enrolled. They were given 5-mg tablets of S-8117 twice-daily. The blood level of oxycodone was monitored at six time points (0, 1, 3, 5, 8 and 12 hours) after the initial dosing (PK/PD phase). In addition, pain intensity was evaluated at the same time points by using CAT (0: none, 1: slight, 2: moderate, 3: severe) and VAS. The dose was increased until pain control was achieved (titration and control phase). The dosing of S-8117 was continued for 7 days.
Correspondence to: W. Koizumi, Department of Internal Medicine, School of Medicine, Kitasato University Department of Pharmacy, Kitasato, Japan.
FIG. 1. Plasma concentration of oxycodone and pain intensity in PK/PD phase.
1090-3801/01/0A0133 + 02 $35.00/0 & 2001 European Federation of Chapters of the International Association for the Study of Pain
Black plate (134,1)
134
as nausea, vomiting, dizziness and constipation were observed, these were tolerable to the patients.
CONCLUSION Possible relationships between PK/PD could be obtained in this pilot study even at 5 mg twice-daily
European Journal of Pain (2001), 5 (Suppl. A)
W. KOIZUMI
ET AL .
for Japanese patients. Furthermore, analgesic efficacy was demonstrated to last over 12 hours with a quick onset of relief after dosing. As the same study has been conducted in other facilities, extensive results from this trial will become available soon.